Withdrawal is a prominent feature of cessation of opioid abuse, and some authors have proposed that it contributes to continuing use of the drug. Since withdrawal is known to produce some behaviors mediated by CRF, it is possible that the withdrawal syndrome is more generally mediated by CRF or other stress-associated factors. To establish the extent of such a relationship, rats will be given chronic opiate treatments; after withdrawal is precipitated by a dose of an opioid antagonist, the presence of various factors associated with stress (e.g., glucocorticoids, CRF, urocortin) will be measured. In addition, the ability of these stress-related factors to elicit behaviors associated with withdrawal will be tested in rats with no history of opioid exposure. Finally, if these early studies indicate a link between some hormone such as CRF and a withdrawal behavior, the effects of this hormone will be tested in a self-administration assay. Monkeys will be trained to self-administer an opioid; before the beginning of a test session, the hormone will be administered and the rate of self- administration will be monitored.